The present invention relates generally to a carrier for the cultivation of animal cells in a fermenter. In this specification any reference to animal cells is intended also to embrace human cells, so that the carrier is thus suitable for the cultivation of human cells and/or animal cells.
In order to provide for growth of adherent animal cells on the fixed surface of a substrate, the substrate must have a surface nature such as to permit the cells satisfactorily to adhere thereto. Surfaces with a positive or a negative electrical charge have been found to be suitable substrates for that purpose. Adhesion and growth factors are also known, for example bivalent cations, fibronectin or serum, which are applied to plastic surfaces in order to promote adhesion and growth of the cells thereon. The electrical charge on the surface of the substrate causes absorption of the adhesion and growth factors on which the cells thus grow. However certain types of cells can themselves synthesize fibronectin and of themselves are therefore capable of growing on charged plastic surfaces, for example diploid fibroblasts. Other cells however necessitate the addition of serum or fibronectin to the culture medium. As will be appreciated however, the addition of serum or fibronectin to the culture medium as adhesion or growth factors give rise to a considerable increase in the cost of cell cultivation ant it is undesirable in many cases, for example in the production of therapeutics.
Adherent animal, including human, cells, in particular connective tissue cells, form a cell growth which permits only a single layer of cells, being what is referred to as a monolayer. That means that the cells can only grow in two dimensions. It is thus necessary to use very substantial surface areas in order to achieve high levels of cell density, which are required in a technical use situation. That is achieved for example by using spherical carrier bodies, also referred to as microcarriers, consisting of cross-linked dextran, with denatured collagen being covalently bonded to the surface thereof. The glutinous dextran bodies are distributed by stirring in the culture medium. The soft consistency of the carrier bodies or microcarriers is intended to reduce damage to or erosion of the grown cells in the event of collisions between the carrier bodies during the stirring operation. If the growth-bearing carrier bodies come into contact with each other and adhere to each other, it is possible to provide for three-dimensional cell culture (reference may be made in this respect to the brochure entitled `Microcarrier cell culture principles & methods` from Pharmacia Fine Chemicals AB, of Uppsala). However, that procedure does not make it possible to achieve controlled three-dimensional cell growth, which is a necessary condition if cell densities as occur in a human or animal body (about 10.sup.9 cells/ml) are to be achieved.
Also known is the hollow fiber module through which the cell culture medium is passed. Cell growth takes place in the interstices between the fibers. When that occurs, a gradient in respect of cell feed with the cell culture medium is formed in the longitudinal direction of the hollow fiber module.
Another known arrangement involes using porous ceramic cartridges through which the cell culture medium is passed. It is also known to provide for microencapsulation of the cells, with cells being encapsulated in Na-alginate and the alginate droplets being enclosed with a polymer network. The alginate is then dissolved out of the network. Those known processes also can only achieve cell densities of the order of magnitude of around 10.sup.7 cells/ml.